Inhibition of binding of the platelet-activating factor AGEPC to platelets by the AGEPC analog rac-3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl 2-thiazolioethyl phosphate (CV-3988).

CV-3988, rac-3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl 2-thiazolioethyl phosphate, is a specific inhibitor of the platelet-activating activity of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine (AGEPC or PAFacether). Concentrations of CV-3988 between 10(-8) and 10(-7) M inhibited AGEPC-induced aggregation of washed human platelets in a dose-related manner (IC50 = 2.9 +/- 1.1 X 10(-8) M CV-3988) whereas concentrations of CV-3988 as high as 4 X 10(-6) M did not diminish platelet aggregation by thrombin or adenosine diphosphate. The binding of [3H] AGEPC to platelets was inhibited by CV-3988 in a concentration-dependent manner (IC50 = 6.7 +/- 1.8 X 10(-8) M). Compared to AGEPC, CV-3988 has a 1000-fold lower affinity for the AGEPC receptor. CV-3988 did not stimulate platelet metabolism of AGEPC as assessed by thin-layer chromatographic analysis of [3H] AGEPC extracted from platelet suspensions after four hours of incubation. Thus these studies indicate that CV-3988 inhibits platelet activation by AGEPC by inhibiting binding of AGEPC to its specific platelet receptor.